This invention relates to the measurement of an electrophysiologic response, and in particular, to the measurement of electrophysiologic responses to auditory stimuli.
In making a diagnosis, it is often useful to have the patient""s cooperation. This is particularly true in the diagnosis of disease involving sensory pathways to the brain. For example, a straightforward way to assess a patient""s hearing is to simply ask the patient whether he can hear particular tones having various frequencies and amplitudes.
In many cases, one takes for granted that a patient will be able to answer such questions. However, in some cases, a patient cannot communicate his perception. This occurs most frequently when the patient is an infant, or when the patient is unconscious. In a veterinary setting, it is rare to encounter a patient that can accurately communicate perception at all.
One approach to evaluating an infant""s hearing is to make a sound and to then measure an evoked response associated with that sound. This evoked response is typically an electrophysiologic signal generated in response to the sound and traveling between the inner ear and the brain along various neural pathways, one of which includes the auditory brainstem. This signal is thus referred to as the xe2x80x9cauditory brainstem-response,xe2x80x9d hereafter referred to as the xe2x80x9cABR.xe2x80x9d
The ABR is typically only a small component of any measured electrophysiologic signal. In most cases, a noise component arising from other, predominantly myogenic, activity within the patient dwarfs the ABR. The amplitude of the ABR typically ranges from approximately 1 microvolt, for easily audible sounds, to as low as 20 nanovolts, for sounds at the threshold of normal hearing. The noise amplitude present in a measured electrophysiologic signal, however, is typically much larger. Typical noise levels range from between 2 microvolts to as much as 2 millivolts. The resulting signal-to-noise ratio thus ranges between xe2x88x926 dB and xe2x88x9240 dB.
One approach to increasing the signal-to-noise ratio is to exploit differences between the additive properties of the ABR and that of the background noise. This typically includes applying a repetitive auditory stimulus (a series of clicks, for example) and sampling the electrophysiologic signal following each such stimulus. The resulting samples are then averaged. The ABR component of the samples add linearly, whereas the background electrophysiologic noise, being essentially random, does not. As a result, the effect of noise tends to diminish with the number of samples.
Since the signal-to-noise ratio depends on the number of samples, one could, in principle, more rapidly measure the ABR by reducing the interval between auditory stimuli. Unfortunately, the impulse response of the human auditory system is not, itself, an impulse. Instead, the response to an impulsive stimulus, such as a click or a tone, is a curve representing a pattern of activity that occupies a finite interval of time. As a result, when the interval between a present stimulus and its preceding stimulus is too short, the response to the preceding stimulus may not have died down before the onset of the response to the present stimulus. This means that a sample intended to capture a response to the present stimulus can be contaminated by the tail end of the response curve for the preceding stimulus. This effect limits how close together two stimuli can be, and hence how quickly a particular signal-to-noise ratio can be achieved.
The invention avoids the foregoing limitation by stimulating the auditory system in a manner that enables an apparatus to remove, from the response due to a particular stimulus, the residual effects of responses due to preceding stimuli. The invention is based on the recognition that by simultaneously stimulating the auditory system with at least two pulse trains having slightly different pulse repetition frequencies, one can average out the responses due to preceding stimuli.
In one aspect, the invention provides for measurement of an electrophysiologic response of a sensory system. The method includes simultaneously stimulating the sensory system with two stimulus trains. The first stimulus train has stimuli temporally separated from each other by a first inter-stimulus interval, whereas the second stimulus train has stimuli separated from each other by a second inter-stimulus interval different from the first inter-stimulus interval. A response signal is then sampled at a first frequency corresponding to the first inter-stimulus interval, thereby obtaining a first response train. The first response train is then processed to suppress a contaminant caused by the second stimulus train.
In one practice of the invention, a second response train is generated by sampling the response signal at a second frequency corresponding to the second inter-stimulus interval. This second response train is then processed to suppress a contaminant attributable to the first stimulus train.
One way to sample a response signal is to define a sequence of sampling windows separated from each other by multiples of the first inter-stimulus interval. During each of a plurality of the sampling windows, samples representative of the electrophysiologic response are obtained. These samples are temporally separated from each other by multiples of an inter-sample interval.
In some practices of the invention, the first and second inter-stimulus intervals can be separated by an integer number of inter-sample intervals. In other practices of the invention, the first and second inter-stimulus intervals can be selected such that all samples from a sampling window are equally likely to be contaminated by a contaminant caused by the second stimulus train. In yet other practices of the invention, the first and second inter-stimulus intervals are selected such that an extent to which a response due to the stimulus train overlaps a sampling window changes between sampling windows.
The invention also includes a data-acquisition system for measuring the response of a sensory system. Such a system includes first and second stimulators simultaneously stimulating the sensory system with first and second stimulus trains. The first stimulus train has stimuli temporally separated from each other by a first inter-stimulus interval. The second stimulus train has stimuli temporally separated from each other by a second inter-stimulus interval different from the first inter-stimulus interval. The system further includes a first sampler for sampling a response signal at a first frequency corresponding to the first inter-stimulus interval, thereby obtaining a first response train, and a processor configured for processing the first response train to suppress a contaminant caused by the second stimulus train.
Additional embodiments include a second sampler for sampling the response signal at a second frequency corresponding to the second inter-stimulus interval, thereby generating a second response train. In these embodiments, the processor is configured to process the second response train by suppressing a contaminant caused by the first stimulus train.
In some embodiments, the first sampler is configured to define a sequence of sampling windows separated from each other by multiples of the first inter-stimulus interval, and to obtain samples representative of the electrophysiologic response during each of a plurality of the sampling windows. The samples are separated from each other by multiples of an inter-sample interval.
In other embodiments, the second sampler is configured to sample the response at a second inter-stimulus interval that differs from the first inter-stimulus interval by an integer number of inter-sample intervals.
In additional embodiments, the second stimulator is configured to generate stimuli separated by a second inter-stimulus interval, the second inter-stimulus interval being selected such that all samples from a sampling window are equally likely to be contaminated by a contaminant caused by the second stimulus train.
Other embodiments include second samplers configured to generate stimuli separated by a second inter-stimulus interval selected such that an extent to which a response due to the second stimulus train overlaps a sampling window changes between sampling windows.
Additional embodiments include a second stimulator configured to generate stimuli separated by a second inter-stimulus interval selected such that the extent of his overlap varies by an integer multiple of the sampling interval.